Partial syntheses of aromatic amides: their anti-urease potential and docking studies.

The aromatic amide: N - p - trans -coumaroyltyramine ( 1 ) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives ( 1a - d ) and previously reported diacetylated product ( 1e ) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product ( 1e ) was found to be the most potent inhibitor with an IC 50 value of 19.5 ± 0.23 μM compared to thiourea used as standard (21.5 ± 0.47 μM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b , 1c , 1d and 1e remained stable throughout the simulation. This study provides insight into the N - p - trans -coumaroyltyramine derivatives ( 1b-e ) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.